CNS inflammation other than multiple sclerosis: how likely is diagnosis?

The incidence, diagnostic landscape, and workload impact of CNS inflammatory diseases other than multiple sclerosis (MS) (CIDOMS) in a tertiary setting is unknown. We describe a retrospective case series of 64 patients identified over a 2-year period (2009–2010) at the Wessex Neurological Centre in the United Kingdom, accounting for 4% of all patients seen at the center. As expected, neurosarcoidosis and neuromyelitis optica (NMO) were the most common diagnoses reached (14% each); other diagnoses singly accounted for <10%. However, the likeliest diagnostic outcome (strikingly, in 25%) was nondiagnosis, despite intensive investigation and a mean follow-up period of 3 years. Undiagnosed patients with CIDOMS represented the largest workload of the neurology center

Lymphopenia in treatment-naive relapsing multiple sclerosis

Lymphopenia accompanies some autoimmune diseases. A number of studies, but not others, have suggested that lymphopenia occurs in treatment-naive multiple sclerosis (MS), so the issue remains unresolved. This is important since lymphopenia may identify an immunologically distinct subset of MS. Also, lymphopenia may emerge as a risk factor for serious viral infections of the brain during dimethyl fumarate treatment. We therefore embarked on a retrospective controlled study of pre-treatment lymphopenia in relapsing M

How do people with multiple sclerosis experience prognostic uncertainty and prognosis communication? A qualitative study

Background: Disease progression in multiple sclerosis (MS) is highly variable and predicting prognosis is notoriously challenging. Patients’ prognosis beliefs, responses to prognostic uncertainty and experiences of prognosis-related communication with healthcare professionals (HCPs) have received little study. These issues have implications for patients’ psychological adjustment and are important in the context of the recent development of personalised prognosis forecasting tools. This study explored patient perspectives on the experience of prognostic uncertainty, the formation of expectations about personal prognosis and the nature of received and desired prognosis communication. Methods: 15 MS patients participated in in-depth semi-structured interviews which were analysed using inductive thematic analysis. Results: Six themes captured key aspects of the data: Experiencing unsatisfactory communication with HCPs, Appreciating and accepting prognostic uncertainty, Trying to stay present-focused, Forming and editing personal prognosis beliefs, Ambivalence towards forecasting the future, and Prognosis information delivery. MS patients report having minimal communication with HCPs about prognosis. Over time MS patients appear to develop expectations about their disease trajectories, but do so with minimal HCP input. Provision of prognosis information by HCPs seems to run counter to patients’ attempts to remain present-focused. Patients are often ambivalent about prognosis forecasting and consider it emotionally dangerous and of circumscribed usefulness.Conclusions: HCPs must carefully consider whether, when and how to share prognosis information with patients; specific training may be beneficial. Future research should confirm findings about limited HCP-patient communication, distinguish predictors of patients’ attitudes towards prognostication and identify circumstances under which prognostic forecasting benefits patients. <br/

Electrical resistivity of pure copper processed by medium-powered laser powder bed fusion additive manufacturing for use in electromagnetic applications

Pure copper is an excellent thermal and electrical conductor, however, attempts to process it with additive manufacturing (AM) technologies have seen various levels of success. While electron beam melting (EBM) has successfully processed pure copper to high densities, laser powder bed fusion (LPBF) has had difficulties achieving the same results without the use of very high power lasers. This requirement has hampered the exploration of using LPBF with pure copper as most machines are equipped with lasers that have low to medium laser power densities. In this work, experiments were conducted to process pure copper with a 200 W LPBF machine with a small laser spot diameter resulting in an above average laser power density in order to maximise density and achieve low electrical resistivity. The effects of initial build orientation and post heat treatment were also investigated to explore their influence on electrical resistivity. It was found that despite issues with high porosity, heat treated specimens had a lower electrical resistivity than other common AM materials such as the aluminium alloy AlSi10Mg. By conducting these tests, it was found that despite having approximately double the resistivity of commercially pure copper, the resistivity was sufficiently low enough to demonstrate the potential to use AM to process copper suitable for electrical applications

The heme-hemopexin scavenging system is active in the brain, and associates with outcome after subarachnoid hemorrhage

Background and Purpose – Long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Free heme is bound by hemopexin (Hpx) and rapidly scavenged by CD91. We hypothesized that heme scavenging in the brain would be associated with outcome after haemorrhage. Methods - Using cerebrospinal fluid (CSF) and tissue from SAH patients and control individuals, the activity of the intracranial CD91-Hpx system was examined using enzyme-linked immunoassays, ultra-high performance liquid chromatography and immunohistochemistry. Results - In control individuals, CSF Hpx was mainly synthesized intrathecally. After SAH, CSF Hpx was high in one-third of cases, and these patients had a higher probability of delayed cerebral ischaemia and poorer neurological outcome. The intracranial CD91-Hpx system was active after SAH since CD91 positively correlated with iron deposition in brain tissue. Heme-Hpx uptake saturated rapidly after SAH, since bound heme accumulated early in the CSF. When the blood-brain barrier was compromised following SAH, serum Hpx level was lower, suggesting heme transfer to the circulation for peripheral CD91 scavenging. Conclusions - The CD91-heme-Hpx scavenging system is important after SAH and merits further study as a potential prognostic marker and therapeutic target

National analyses on survival in Maltese adult patients on renal replacement therapy started during 2009–2012

Chronic kidney disease patients on maintenance dialysis (CKD 5D) experience major morbidity and mortality. No data on survival in Maltese dialysis patients exist; therefore, the aim of this study was to rigorously examine survival statistics in a complete cohort of Maltese CKD 5D patients. The study population was comprised of all incident chronic patients (N=328) starting dialysis at the renal unit, Mater Dei hospital, Msida, Malta, for 4 consecutive years (2009–2012). Each yearly cohort was analysed in detail up to 31st December 2017, providing up to 8 years follow-up. Demographics (male 65%; female 35%), aetiology of renal failure (diabetic kidney disease: n=191; 58.2%), comorbidities, transplant status, and death were documented. Data collection and follow up were completed and statistical analysis was performed on the aggregated cohorts with SPSS version 23 with censoring up to 31st December 2017. The cumulative adjusted 5-year overall survival in Maltese CKD 5D patients was 0.36 and 0.25 at 8 years. No statistical difference was observed according to the year of starting dialysis. Cox regression analysis showed that age and transplant status influenced survival. The unadjusted hazard of death increased by 3% for every 1-year increase in age and was increased by 7% if the patient did not receive a transplant, and overall 22% (n=72) of the entire cohort eventually received transplants. This study reports an approximate 65% mortality at 5 years in Maltese haemodialysis patients, a poor prognosis that, despite optimal medical management, is consistent with worldwide reports.peer-reviewe

Electrical resistivity of additively manufactured AlSi10Mg for use in electric motors

Additive manufacturing (AM) opens up a design freedom beyond the limits of traditional manufacturing techniques. Electrical windings created through AM could lead to more powerful and compact electric motors, but only if the electrical properties of the AM printed part can be shown to be similar to conventionally manufactured systems. Until now, no study has reported on the suitability of AM parts for electrical applications as there are few appropriate materials available to AM for this purpose. AlSi10Mg is a relatively good electrical conductor that does not have the same reported issues associated with processing pure aluminium or copper via selective laser melting (SLM). Here, experiments were conducted to test the effects of geometry and heat treatments on the resistivity of AlSi10Mg processed by SLM. It was found that post heat treatments resulted in a resistivity that was 33% lower than the as-built material. The heat treatment also eliminated variance in the resistivity of as-built parts due to initial build orientation. By conducting these tests, it was found that, with this material, there is no penalty in terms of higher resistivity for using AM in electrical applications, thus allowing more design freedom in future electrical applications

Simulating movement devices used in hospital evacuation

In hospitals, the evacuation of those with severe movement impairments can be highly problematic for the patients, for the staff and for other evacuees. It is critical to understand the performance of horizontal and vertical evacuation procedures, including the means by which people with reduced mobility can be assisted during stair descent. Microsimulation modelling provides a useful tool to assess evacuation strategies, given the challenges of preparing and transporting patients in need of on-going care and the unfeasibility of real evacuation drills. However, current simulation models typically focus on the movement of individual agents, not the staff-patient interactions and sizable equipment required to carry out assisted evacuation. To address this, the buildingEXODUS evacuation model has been enhanced to represent moving objects in addition to moving individual agents. This paper describes the modelling theory behind this development, where dedicated data has been applied to enable the explicit specification of evacuation devices, operated by agents (for instance, representing the vertical travel speeds achieved—with averages ranging between 0.6 m/s and 0.84 m/s—when employing different movement devices). Algorithms are presented that calculate the movement of devices along corridors, through doorways and in stairway descent, including a method of geometric decomposition of the available hospital evacuation routes. This new functionality addresses the key evacuation components of repeated patient collection and has numerous applications, both in simulating hospital evacuation and in representing evacuation of other premises that include people with reduced mobility. Examination of the performance of this functionality found it predicated performance within 6% of expectation. Once further testing is completed, the resultant tool can be used to significantly enhance planning and diagnostic capabilities related to the evacuation of hospital and other healthcare facilities

Structural basis for inflammation-driven shedding of CD163 ectodomain and tumor necrosis factor-α in macrophages

The haptoglobin-hemoglobin receptor CD163 and proTNF-α are transmembrane macrophage proteins subjected to cleavage by the inflammation-responsive protease ADAM17. This leads to release of soluble CD163 (sCD163) and bioactive TNF-α. Sequence comparison of the juxtamembrane region identified similar palindromic sequences in human CD163 ((1044)Arg-Ser-Ser-Arg) and proTNF-α ((78)Arg-Ser-Ser-Ser-Arg). In proTNF-α the Arg-Ser-Ser-Ser-Arg sequence is situated next to the previously established ADAM17 cleavage site. Site-directed mutagenesis revealed that the sequences harbor essential information for efficient cleavage of the two proteins upon ADAM17 stimulation. This was further evidenced by analysis of mouse CD163 that, like CD163 in other non-primates, does not contain the palindromic CD163 sequence in the juxtamembrane region. Mouse CD163 resisted endotoxin- and phorbol ester-induced shedding, and ex vivo analysis of knock-in of the Arg-Ser-Ser-Arg sequence in mouse CD163 revealed a receptor shedding comparable with that of human CD163. In conclusion, we have identified an essential substrate motif for ADAM17-mediated CD163 and proTNF-α cleavage in macrophages. In addition, the present data indicate that CD163, by incorporation of this motif in late evolution, underwent a modification that allows for an instant down-regulation of surface CD163 expression and inhibition of hemoglobin uptake. This regulatory modality seems to have coincided with the evolution of an enhanced hemoglobin-protecting role of the haptoglobin-CD163 system in primate